rs587780781
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000265433.8(NBN):c.279G>A(p.Ser93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,900 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 2 hom. )
Consequence
NBN
ENST00000265433.8 synonymous
ENST00000265433.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0630
Genes affected
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 8-89981416-C-T is Benign according to our data. Variant chr8-89981416-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 136044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.063 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.279G>A | p.Ser93= | synonymous_variant | 3/16 | ENST00000265433.8 | NP_002476.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.279G>A | p.Ser93= | synonymous_variant | 3/16 | 1 | NM_002485.5 | ENSP00000265433 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152142Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000187 AC: 47AN: 251382Hom.: 2 AF XY: 0.000191 AC XY: 26AN XY: 135876
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GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461758Hom.: 2 Cov.: 31 AF XY: 0.0000399 AC XY: 29AN XY: 727174
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74304
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 05, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 08, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2014 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Aug 17, 2021 | - - |
Microcephaly, normal intelligence and immunodeficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at